Triphosgene → HCID 24991078, compound

To a vigourously stirred mixture of N-[(1S)-1-(3-aminophenyl)ethyl]-6-chloropyrazin-2-amine (49 mg, 0.2 mmol) and saturated aqueous sodium hydrogen carbonate (1.2 mL) in dichloromethane (1.2 mL) was added triphosgene (20 mg, 0.067 mmol) in one portion and the mixture was stirred for 3 hours. After this time 5-methylpyridin-3-amine (60 mg, 0.55 mmol) was added and the mixture was stirred for 17 hours. The mixture was then diluted with dichloromethane (20 mL) and was washed with brine (20 mL), dried (MgSO4) and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (20 mL) and extracted with dilute aqueous hydrochloric acid (0.5M, 3×15 mL). The combined acidic extracts were basified to pH 5 with solid potassium hydroxide and were then extracted with dichloromethane (3×20 mL). The combined organic extracts were washed with brine (20 mL), dried (MgSO4) and concentrated under reduced pressure to give an orange oil which was purified by passage through a column of Sephadex with methanol as eluant. N-(3-{(1S)-1-[(6-Chloropyrazin-2-yl)amino]ethyl}phenyl)-N′-(5-methylpyridin-3-yl)urea (32 mg, 42%) was obtained as a colourless foam.

1. stirringthe mixture was stirred for 17 hours
2. washwas washed with brine (20 mL)
3. dry with materialdried (MgSO4)
4. concentrationconcentrated under reduced pressure
5. dissolutionThe residue was dissolved in ethyl acetate (20 mL)
6. extractionextracted with dilute aqueous hydrochloric acid (0.5M, 3×15 mL)
7. extractionwere then extracted with dichloromethane (3×20 mL)
8. washThe combined organic extracts were washed with brine (20 mL)
9. dry with materialdried (MgSO4)
10. concentrationconcentrated under reduced pressure
11. customto give an orange oil which
12. customwas purified by passage through a column of Sephadex with methanol as eluant

ORD record

ord-1650cc28eacd4b9ebd20fd51d4cb1a1f

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08461161B2